Synthesis and evaluation of spumigin analogues library with thrombin inhibitory activity

Žula, Aleš (avtor), Będziak, Izabela (avtor), Kikelj, Danijel (avtor), Ilaš, Janez (avtor)

Spumigins are marine natural products derived from cyanobacteria Nodularia spumigena, which mimics the structure of the D-Phe-Pro-Arg sequence and is crucial for binding to the active site of serine proteases thrombin and factor Xa. Biological evaluation of spumigins showed that spumigins with a (2S,4S)-4-methylproline central core represent potential lead compounds for the development of a new structural type of direct thrombin inhibitors. Herein, we represent synthesis and thrombin inhibitory activity of a focused library of spumigins analogues with indoline ring or L-proline as a central core. Novel compounds show additional insight into the structure and biological effects of spumigins. The most active analogue was found to be a derivative containing L-proline central core with low micromolar thrombin inhibitory activity.

• Jezik: Angleški jezik
• Ključne besede: marine products, natural peptides, peptidomimetics, thrombin inhibition
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2018
• Št. strani: 20 str.
• Številčenje: Vol. 16, iss. 11, art. 413
• PID: 20.500.12556/RUL-125357
• UDK: 577
• ISSN pri članku: 1660-3397
• DOI: 10.3390/md16110413
• COBISS.SI-ID: 39787781
• Datum objave v RUL: 12.03.2021

Gradivo je del revije

• Naslov: Marine drugs
• Skrajšan naslov: Mar. drugs
• Založnik: MDPI
• ISSN: 1660-3397
• COBISS.SI-ID: 23578841

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 12.03.2021

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: biokemija, morski proizvodi, naravni peptidi, inhibicija trombina

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0208
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

• Financer: EC - European Commission
• Program financ.: FP7
• Številka projekta: 245137
• Naslov: Exploring Marine Resources for Bioactive Compounds: From Discovery to Sustainable Production and Industrial Applications
• Akronim: MAREX